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A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan He Rong Liu Yuan Xue Yuan Quan Rongying Shi xueying yang Qing Lin Xun Sun Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer therapy.However,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).Here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for melanoma.The system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the combination.Our study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)infiltration.The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment.This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy Tumor immune microenvironment

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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao xueying yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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On the parameterized complexity of minimum/maximum degree vertex deletion on several special graphs

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Frontiers of Computer Science 2023年第4期17卷 97-107页

作者： Jia LI Wenjun LI Yongjie yang xueying yang School of Information Engineering Hunan Industry PolytechnicChangsha 410036China Hunan Provincial Key Laboratory of Intelligent Processing of Big Data on Transportation School of Computer and Communication EngineeringChangsha University of Science and TechnologyChangsha 410015China Chair of Economic Theory Saarland UniversitySaarbrücken 66123Germany

In the minimum degree vertex deletion problem,we are given a graph,a distinguished vertex in the graph,and an integer κ,and the question is whether we can delete at most κ vertices from the graph so that the distinguished vertex has the unique minimum degree.The maximum degree vertex deletion problem is defined analogously but here we want the distinguished vertex to have the unique maximum degree.It is known that both problems areΨ-hard and fixed-parameter intractable with respect to some natural parameters.In this paper,we study the(parameterized)complexity of these two problems restricted to split graphs,p-degenerate graphs,and planar graphs.Our study provides a comprehensive complexity landscape of the two problems restricted to these special graphs.

关键词： minimum degree maximum degree vertex deletion split graphs planar graphs parameterized complexity

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The Critical Role of Fillers in Composite Polymer Electrolytes for Lithium Battery

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Nano-Micro Letters 2023年第5期15卷 339-375页

作者： xueying yang Jiaxiang Liu Nanbiao Pei Zhiqiang Chen Ruiyang Li Lijun Fu Peng Zhang Jinbao Zhao College of Energy Xiamen UniversityXiamen 361102People’s Republic of China State Key Laboratory of Physical Chemistry of Solid Surfaces Collaborative Innovation Centre of Chemistry for Energy MaterialsState-Province Joint Engineering Laboratory of Power Source Technology for New Energy VehicleEngineering Research Center of Electrochemical TechnologyMinistry of EducationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005People’s Republic of China College of Energy Nanjing Technical UniversityNanjing 211816People’s Republic of China

With excellent energy densities and highly safe performance,solidstate lithium batteries(SSLBs)have been hailed as promising energy storage devices.Solid-state electrolyte is the core component of SSLBs and plays an essential role in the safety and electrochemical performance of the cells.Composite polymer electrolytes(CPEs)are considered as one of the most promising candidates among all solid-state electrolytes due to their excellent comprehensive performance.In this review,we briefly introduce the components of CPEs,such as the polymer matrix and the species of fillers,as well as the integration of fillers in the polymers.In particular,we focus on the two major obstacles that affect the development of CPEs:the low ionic conductivity of the electrolyte and high interfacial impedance.We provide insight into the factors influencing ionic conductivity,in terms of macroscopic and microscopic aspects,including the aggregated structure of the polymer,ion migration rate and carrier concentration.In addition,we also discuss the electrode-electrolyte interface and summarize methods for improving this interface.It is expected that this review will provide feasible solutions for modifying CPEs through further understanding of the ion conduction mechanism in CPEs and for improving the compatibility of the electrode-electrolyte interface.

关键词： Composite polymer electrolytes Fillers Ionic conductivity Electrode-electrolyte interface

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Radiotherapy delivery error detection with electronic portal imaging device (EPID)-based in vivo dosimetry

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Chinese Medical Journal 2023年第8期136卷 998-1000页

作者： xueying yang Lisheng Geng David Huang Kaiwen Li Hongqing Zhuang Jing Cai Ruijie yang School of Physics Beihang UniversityBeijing 102206China Department of Radiation Oncology Peking University Third HospitalBeijing 100191China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of Medicine and EngineeringBeihang UniversityBeijing 100191China Medical Physics Graduate Program Duke Kunshan UniversityKunshanJiangsu 215316China Medical Management Department CAS Ion Medical Technology Co.Ltd.Beijing 100190China Department of Health Technology and Informatics The Hong Kong Polytechnic UniversityHong Kong 999077China

To the Editor:Due to the highly complex nature of intensity-modulated radiotherapy(IMRT)planning and delivery,patient specific quality assurance(PSQA)should be implemented to assure the reliability of treatment delive... 详细信息

关键词： IMRT treatment vivo

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A non-metabolic function of hexokinase 2 in small cell lung cancer:promotes cancer cell stemness by increasing USP11-mediated CD133 stability

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Cancer Communications 2022年第10期42卷 1008-1027页

作者： Juhong Wang Fei Shao Yannan yang Wei Wang xueying yang Renda Li Hong Cheng Sijin Sun Xiaoli Feng Yibo Gao Jie He Zhimin Lu Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Laboratory of Translational Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116P.R.China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310029P.R.China Cancer Center Zhejiang UniversityHangzhouZhejiang 310029P.R.China

Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor grow

关键词： HK2 metabolic enzyme non-metabolic function cancer stem-like cell CD133 USP11 ubiquitylation SCLC

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Development of robust perovskite single crystal radiation detectors with high spectral resolution through synergetic trap deactivation and self-healing

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InfoMat 2023年第9期5卷 26-37页

作者： Lixiang Wang Yilong Song Liqi Li Liting Tao Minxing Yan Weihui Bi xueying yang Yuan Sun Qingfeng Dong Deren yang Yanjun Fang State Key Laboratory of Silicon Materials and School of Materials Science and Engineering Zhejiang UniversityHangzhouthe People's Republic of China State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchunthe People's Republic of China Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuanthe People's Republic of China

Organic-inorganic halide perovskite single crystals(SCs)are promising materials for detecting ionizing radiation owing to their outstanding photoelectric conversion capability and inexpensive solution processability.However,the accuracy and stability of the detectors have been limited due to the charge traps and defects in SCs,especially when operated under high-precision photon-counting mode for energy spectrum acquisition.Here,we proposed a trap freezing deactivation route,which obviously suppressed dark current and noise by up to 97%and 92%,respectively.Furthermore,the bulk ion migration effect was essential for the ability to instantly self-heal defects induced by radiation damage at temperatures down to30C.Consequently,the detector exhibits a record high energy resolution of 7.5%at 59.5 keV for 241Amγ-ray source,which is the best solution-processed semiconductor radiation detectors at the same energy range.In addition,the detector maintains over 90%of its initial performance after 9 months of storage when tested in the air.Our results will represent a revision of the paradigm that high-spectral-resolution and robust radiation detectors can only be realized with high temperature grown inorganic semiconductor single crystals.

关键词： energy resolution perovskite single crystal photon counting radiation detector self-healing stability

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Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome

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Genes & Diseases 2022年第6期9卷 1662-1673页

作者： Jia Jiao Li Wang Fenfen Ni Mo Wang Shipin Feng Xiaojie Gao Han Chan xueying yang Hao Lee Huan Chi Xuelan Chen Daoqi Wu Gaofu Zhang Baohui yang Anshuo Wang Qin yang Junli Wan Sijie Yu Xiaoqin Li Mei Wang Xiaofeng Chen Xianying Mai Xiongzhong Ruan Haiping yang Qiu Li Department of Nephrology Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400015PR China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610091PR China Department of Nephrology Sheen Children’s HospitalShenzhenGuangdong 518034PR China Centre for Lipid Research&Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated Hospital Chongqing Medical UniversityChongqing 400016PR ChinaJohn Moorhead Research LaboratoryCentre for NephrologyUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon WC1E 6BTUnited Kingdom

Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome(NS)of different etiologies is critical for early clinical guidance.We employed whole-exome sequencing(WES)to detect monogenic causes of NS in a multicenter cohort of 637 patients.In this study,a genetic cause was identified in 30.0%of the idiopathic steroid-resistant nephrotic syndrome(SRNS)patients.Other than congenital nephrotic syndrome(CNS),there were no significant differences in the incidence of monogenic diseases based on the age at manifestation.Causative mutations were detected in 39.5%of patients with focal segmental glomerulosclerosis(FSGS)and 9.2%of those with minimal change disease(MCD).In terms of the patterns in patients with different types of steroid resistance,a single gene mutation was identified in 34.8%of patients with primary resistance,2.9%with secondary resistance,and 71.4%of children with multidrug resistance.Among the various intensified immunosuppressive therapies,tacrolimus(TAC)showed the highest response rate,with 49.7%of idiopathic SRNS patients achieving complete remission.Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern,and only 31.4%of patients with monogenic disease achieved a partial remission on TAC.During an average 4.1-year follow-up,21.4%of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease(ESRD).Collectively,this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients,especially those with primary and/or multidrug resistance.

关键词： Clinical phenotypes Genetic phenotypes Multicenter cohort Nephrotic syndrome Pediatric Whole-exome sequencing

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Detector-grade perovskite single-crystal wafers via stress-free gel-confined solution growth targeting high-resolution ionizing radiation

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Light(Science & Applications) 2023年第5期12卷 754-765页

作者： Yilong Song Lixiang Wang Yongqiang Shi Weihui Bi Jianwu Chen Mingwei Hao Anran Wang xueying yang Yuan Sun Fan Yu Liansheng Li Yanjun Fang Deren yang Qingfeng Dong State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012China State Key Laboratory of Silicon Materials and School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027China Beijing Institute of Control Engineering Beijing 100190China Science and Technology on Space Intelligent Control Laboratory Beijing 100190China Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan 030024China

Solution-processed organic‒inorganic halide perovskite(OIHP)single crystals(SCs)have demonstrated great potential in ionizing radiation detection due to their outstanding charge transport properties and low-cost preparation.However,the energy resolution(ER)and stability of OIHP detectors still lag far behind those of melt-grown inorganic perovskite and commercial CdZnTe counterparts due to the absence of detector-grade high-quality OIHP SCs.Here,we reveal that the crystallinity and uniformity of OIHP SCs are drastically improved by relieving interfacial stress with a facial gel-confined solution growth strategy,thus enabling the direct preparation of large-area detector-grade SC wafers up to 4 cm with drastically suppressed electronic and ionic defects.The resultant radiation detectors show both a small dark current below 1 nA and excellent baseline stability of 4.0×10^(-8) nA cm^(-1) s^(-1) V^(-1),which are rarely realized in OIHP detectors.Consequently,a record high ER of 4.9% at 59.5 keV is achieved under a standard 241Am gamma-ray source with an ultralow operating bias of 5 V,representing the best gamma-ray spectroscopy performance among all solution-processed semiconductor radiation detectors ever reported.

关键词： resolution confined stress

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文旅融合背景下城市公共阅读空间建设路径探析

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河南图书馆学刊 2024年第5期44卷 103-104,126页

作者：杨雪英山东省政协文史馆山东济南250011

城市书房是一种新型的公共阅读空间,有助于打通公共文化服务的“最后一公里”,开展相关建设工作是有关部门和机构推动公共文化服务事业高质量发展的有效途径。文章以济南市的泉城书房为例,对其运营模式、资金保障和布局情况等进行了梳理... 详细信息

城市书房是一种新型的公共阅读空间,有助于打通公共文化服务的“最后一公里”,开展相关建设工作是有关部门和机构推动公共文化服务事业高质量发展的有效途径。文章以济南市的泉城书房为例,对其运营模式、资金保障和布局情况等进行了梳理,提出了科学选址、因地制宜、跨界合作、技术赋能等文旅融合背景下的泉城书房建设路径,以期为城市公共阅读空间的规划建设提供参考。

关键词：文旅融合公共阅读空间泉城书房

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